Features of IL-8 and IL-10 production in pregnant women with urogenital infections

Objective. To determine features of IL-8 and IL-10 production in pregnant women with urogenital infections (UGI) in the first trimester, and their role for prognosis of obstetric and perinatal complications.

Materials and methods. The prospective cohort study included 98 pregnant women in the first trimester, of which 66 patients were diagnosed with genital infections (GI) — main group, 8 had genital infections combined with urinary tract infection — comparison group, and 24 pregnant women without urogenital infection formed the control group. Concentration of IL-8 and IL-10 in the blood serum was determined by the enzyme immunoassay method. The characteristics of the course of pregnancy, childbirth, and the condition of the newborns were assessed.

Results. Systemic production of IL-8 and IL-10 in the first trimester of pregnancy does not depend on the presence of genital infection. Recurrence in patients of the main group is preceded by higher serum levels of IL-8, determined in pregnant women in the first trimester with diagnosed GI (p=0.0001; Z=3.794). It is possible to predict the development of a relapse of GI in the second-third trimester (AUC=0.809; 95 % CI 0.694-0.895; p=0.0001) at IL-8 concentration of more than 7.6 pg/ml in pregnant women with GI in the first trimester with a sensitivity of 82.4% and a specificity of 83.7%.

The formation of placental insufficiency in patients of the main and control groups was preceded by higher concentrations of IL-8 in the first trimester of pregnancy (pо = 0.0001; Z=3.871; pк =0.025; Z=2.235). In pregnant women without UGI with a serum IL-8 level of more than 14.15 pg/ml, it is possible to predict the development of placental insufficiency with a sensitivity of 100% and a specificity of 95.5% (AUC=0.977; 95% CI 0.817-0.988; p=0.0001).

Development of threatened miscarriage was associated with higher serum levels of IL-10 in the first trimester of pregnancy (pо=0.007; Z=2.682; pк =0.031; Z= 2.153) in the main and control groups.

Conclusion. Determination of IL-8 and IL-10 levels in the blood serum of women in the first trimester of pregnancy allows predicting the development of gestational complications such as threatened miscarriage, development of genital infection and placental insufficiency, development of genital infection and placental insufficiency, timely formation of risk groups for medical prevention of these complications and, thereby, improvement of maternal and perinatal outcomes.

1. Tian M, Li Q, Zheng T, Yang S, Chen F, Guan W, Zhang S. Maternal microbe-specific modulation of the offspring microbiome and development during pregnancy and lactation. Gut Microbes. 2023;15(1): 22-26. DOI: https://doi.org/10.1080/19490976.2023.2206505

2. Fu Y, Tang L, Hu M, Xiang ZY, Hu Y, Liu Q. Changes of serum interleukin-6 in healthy pregnant women and establishment of relevant reference intervals. Clin. Chim. Acta. 2020;50(2):116-119. DOI: https://doi.org/10.1016/j.cca.2019.12.013

3. Spence T, Allsopp PJ, Yeates AJ, Mulhern MS, Strain JJ, McSorley EM. Maternal serum cytokine concentrations in healthy pregnancy and preeclampsia. Journal of pregnancy. 2021; 2021(1): 2-26. DOI: https://doi.org/10.1155/2021/6649608//2021:6649608

4. Cakir SC, Dorum BA, Koksal N, Ozkan H. The effects of maternal preeclampsia on inflammatory cytokines and clinical outcomes in premature infants. Pakistan Journal of Medical Sciences. 2020;36(2):26-31. DOI: https://doi.org/10.12669/pjms.36.2.1316

5. Cobo T, Aldecoa V, Figueras F, Herranz A, Ferrero S, Izquierdo M, et al. Development and validation of a multivariate model for predicting spontaneous preterm birth and amniotic microbial invasion in women with preterm labor. ObstetGynecol. 2020; 223(3):421. DOI: http://dx.doi.org/10.1016/j.ajog.2020.02.049

6. Tapilskaya NI, Savicheva AM, Shalepo KV, Budilovskaya OV, Gzgzyan AM, Bespalova ON, et al. Local Immune Biomarker Expression Depending on the Uterine Microbiota in Patients with Idiopathic Infertility. Int J Mol Sci. 2023; 24(8):757. DOI: http://dx.doi.org/10.3390/ijms24087572

7. Cappelletti M, Presicce P, Kallapur SG. Immunobiology of acute chorioamnionitis. Front Immunol. 2020;11:649. DOI: http://dx.doi.org/10.3389/fimmu.2020.00649

8. Peterson LS, Stelzer IA, Tsai AS, Ghaemi MS, Han X, et al. Multiomic immune clockworks of pregnancy. Semin. Immunopathol. 2020;42: 397-412. DOI: https://doi.org/10.1007/s00281-019-00772-1

9. Jeong S, Cho WК, Jo Y. Effects of immune checkpoint proteins, cytokines and microbiome on patients with cervical insufficiency and preterm labor. Front. Immunol 2023;14:1-10. DOI: https://doi.org/10.3389/fimmu.2023.1228647

10. Dudareva JA, Seroshtanova DN. The role of endothelial dysfunction and subclinical inflammation in the development of obstetric and perinatal complications in diabetes mellitus patients. Acta Biomedica Scientifica (East siberian biomedical journal). 2021;6(3):9-16. (In Russ.). DOI: http://dx.doi.org/10.29413/ABS.2021-6.3.1

11. Baud A, Hillion KH, Plainvert C, Tessier V, Tazi A, Mandelbrot L, et al. Microbial diversity in the vaginal microbiota and its link to pregnancy outcomes. Scientific Reports. 2023; 13(1):9061. DOI: http://dx.doi.org/10.1038/s41598-023-39583-8

12. Soleeva N, Gulshaido M, Nasimova N. Placental insufficiency: modern methods of diagnosis, treatment and its impact on the health of the fetus and child. Innovative research in the modern world: theory and practice. 2024; 3(8): 25-28. (In Russ.). DOI: https://doi.org/10.5281/zenodo.12703983

13. Shadaeva YA, Guryeva MG, Nikolaeva NV, Yevtushenko YA, Shadeeva VA. Prediction of the risk of intrauterine fetal infection in very early and early preterm birth induced by rupture of membranes. Obstetrics Gynecology and Reproduction. 2020;14(4):490-501. (In Russ.). DOI: https://doi.org/10.17749/2313-7347/ob.gyn.rep.2020.110

14. Marochko TY, Levanova LA, Kolesnicova NB, Surina MN, Karelina OB, Kopytova KR. Clinical and morphological parallels in microbial colonization of the placenta. Fundamental and clinical medicine. 2019;2(4):32-37. (In Russ.). DOI: https://doi.org/10.23946/2500-0764-2019-4-4-32-37

15. Belokrinitskaya TE, Vitkovsky YA, Frolova NI. The role of cytokines and interferons during pregnancy. Fundamental and clinical medicine. 2024;9(3):98-108. (In Russ.). DOI: https://doi.org/10.23946/2500-0764-2024-9-3-98-108

16. Vilotić A, Nacka-Aleksić M, Pirković A, Bojić-Trbojević Ž, Dekanski D, Jovanović Krivokuća M. IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int J Mol Sci. 2022 Nov 23;23(23):14574. DOI: https://doi.org/10.3390/ijms232314574